The effect of blood-brain barrier (BBB) breakdown to proteins on the water content of brain tissue was studied in rabbits subjected to unilateral bolus injection of the animal's own blood into the internal carotid artery under pressure. The BBB was assessed with Evans Blue (EB) tracer and with the immunohistochemical peroxidase-antiperoxidase method designed for demonstration of rabbit serum proteins. Also, the penetration of horseradish perioxidase (HRP) tracer, as well as the morphology of the brain tissue, was studied on the electron microscopic level. Water content of the brain tissue was evaluated with a modified specific gravity (SG) method. The results of this study indicate that breakdown of the BBB, allowing entry of serum proteins into extracellular spaces of brain parenchyma, free of any evidence of injury, is associated with a significant increment in water content of this tissue, signifying development of vasogenic brain edema. This type of edema is clinically the most common and important. It is associated with brain tumors, trauma, inflammatory processes and various forms of stroke. Elucidation of the factors responsible for the development of brain edema is imperative in the proper treatment of neurological conditions associated with edema.